Current pre-operative and intraoperative imaging techniques fail to adequately define the microscopic extent of breast cancers. As a result, 17-59% of lumpectomy patients have unrecognized tumor discovered at their resection margins and require additional surgical procedures that increase patient discomfort and health care costs. This non-randomized, single center Phase II clinical trial will study the efficacy of an intraoperative fluorescence imaging system developed by Lumicell Diagnostics for identifying residual cancer at lumpectomy margins in breast cancer patients. The technology consists of a molecular imaging agent (LUM015) that emits fluorescence after activation by cancer associated enzymes, and a compact profile, hand-held device that detects the fluorescence emission of the agent with single-cell sensitivity. The safety of the imaging agent LUM015 will be tested in a Phase I trial at Duke University Medical Center. Our trial will be divided into 2 sections: Phase IIA: 12 patients enrolled to (1) investigate that lumpectomy cavity regions showing fluorescence contain cancer and (2) assess the optimal injection time point; and Phase IIB: 105 patients enrolled to evaluate efficacy of the technology in reducing positive margin rates by excising tissue the detection system identifies as cancerous. All patients will be injected with LUM015 at defined time points 24-48 hours before surgery. Patients will undergo standard lumpectomy surgery with removal of gross tumor with standard margins. The lumpectomy cavity will then be scanned with the hand-held imaging device and sites of high fluorescence noted. Per standard of care, an additional 5-10 mm final margin strip of tissue will be excised from all walls of the lumpectomy cavity for histology testing to look for microscopic residual cancer. In Phase IIA, areas of fluorescence identified in specific quadrants of the lumpectomy cavity will be correlated with the histological findings in the additional final shaved margin tissue taken from that quadrant. These data will be used to (1) characterize the ability of the imaging system to accurately distinguish tumor from benign tissue in the lumpectomy cavity and (2) identify the optimum time point for LUM015 injection. In Phase IIB, patients will have standard lumpectomy surgery with imaging of the cavity walls and standard resection of 5-10 mm of final margin tissue from all cavity walls. The cavity will then be imaged again and an additional strip of tissue taken from any portions of the cavity wall that still show high fluorescence. Rates of positive margins for standard lumpectomy and standard final margins vs. lumpectomy and final margin resection guided by fluorescence will be compared. These data will be used to evaluate the efficacy of the detection system for providing accurate, real time information on microscopic margin status.